Manufacture of medicinal capsules



Oct. 29, 1940. P. s. PITTENGER MANUFACTURE OF IEDICINAL CAPSULES FiledDec. 19, 1936' 4 Sheets-Sheet 2 ATTORNEYS Oct. 29, 1940. P. s. PITTENGERMANUFACTURE OF MEDICINAL CAPSULES 4 Sheets-Sheet 5 Filed. Dec. 19, 1936INVENTOR ATTORNEYS //4 mA////////////// Wm am Patented Oct. 29, 1940 1PATENT OFFICE MANUFACTURE OF MEDICINAL CAPSULES Paul S. Pittenger,Philadelphia, Pa., assignor to Sharp & Dohme, Incorporated,Philadelphia, Pa., a corporation of Maryland Application December 19,1936, Serial No. 116,690

' 4 Claims.

This invention relates to new and improved processes and apparatus forthe continuous production of medicinal capsules having coatings of atough, tenacious, soluble, elastic sheet material 5 and containingaccurately measured and predetermined amounts of a liquid medicinalsubstance hermetically sealed therein.

It is important, in producing medicinal capsules containing a liquidmedicinal compound that the quantity of the medicinal compound beaccurately determined and that the proper amount of the compound beintroduced into each capsule. It is also important to be sure that thecapsules are properly sealed, and that air be excluded from thecapsules, so that they contain no air bubbles. The present inventionprovides a process and apparatus by which capsules meeting all theserequirements may be continuously produced in an economical manner, witha minimum of waste and a minimum of improperly formed capsules whichmust be rejected and treated for the recovery/of the material.

It has been customary for a long time, in the production ofliquid-containing capsules, to use soluble sheet gelatin, to place asheet of the gelatin on a female mold member having raised edges andhaving spaced openings therein, to pour the desired amount of liquid tobe incapsulated on the sheet, then to place a second sheet over theliquid in a manner which eliminates all air bubbles, and with the edgeof the top sheet overlapping the raised edges of the lower sheet, andthen to place av similar mold member, having openings opposite those inthe lower member, on top of the top sheet, and place the mold members ina hydraulic press, where pressure is applied. As the mold members areforced together, the liquid, not being able to escape, pushes theelastic gelatin in both directions into the openings, thus forming theupper and lower halves of the capsules, and the motion of the moldmembers finally results in the cutting of the gelatin and the forcing ofthe edges together, thus hermetically sealing the capsules. In suchprocesses, it frequently happens that capsules produced near the centerof the mold members have more liquid incapsulated in them than thecapsules located near the periphery of the mold members, due to the factthat the gelatin when placed upon the lower mold member does not liefiat, and there, is a tendency for a bulge to form between the twosheets of gelatin near the center. Also, where differences in thicknessor tensile strength of the gelatin occur, there is a tendency to formlopsided capsules, with portions of the coating unduly stretched, whichfrequently must be discarded.

It has also been proposed to form liquid filled capsules by a continuousprocess in which two sheets of coating material, for example, gelatin, 5are fed in converging paths over rotatable mold members having a numberof mold openings, similar to those previously used in the process abovedescribed, and, by a suitable ejecting device, which forces a measuredamount of liquid 10 on to the gelatin positioned over the mold openings,to form suitable half sections of capsules in corresponding positions ineach of the converging sheets of gelatin, with subsequent uniting ofthese half sections and sealing of the edges thereof. Such a processdepends largely upon proper control of the fluid ejected for control ofthe amount of liquid incapsulated.

According to the present invention, liquid filled capsules are producedcontinuously by preforming depressions or recesses in correspondingpositions in each of two converging sheets of coating material, such asgelatin, by means of a vacuum, the size of the depressions or recwsesbeing determined by the size and shape of the mold openings into whichthe coating material is drawn by the vacuum, and by proper control overthe thickness of the sheets used. The preformed -recesses or depressionsin the sheets are filled with liquid to be incapsulated by passing thecon- 80 tinuously moving sheets with the depressions or recesses formedtherein through a body of liquid in a manner such that each recess ordepression is completely filled with liquid, with complete eliminationof air, and at the point of convergence of the two sheets, cutting andsealing the coating material around each of the capsules formed by theconvergence of two corresponding recesses or depressions each filledwith liquid.

In this way, capsules of various sizes and shapes may be readilyproduced, the size and shape of the capsule being determinedby the sizeand shape of the mold opening into which the coating, material is drawnby the vacuum, and by the thickness of the coating material. Thus greataccuracy can be achieved in the predetermination of the amount of liquidto be incapsulated in each capsule, as the mold opening may be readilymade of any desired shape or size, and as the thickness of the coatingmaterial maybe readily 5o controlled with a tolerance of 0.001 inch orless.

The sheet material which is employed in coating the capsules mayadvantageously be sheet gelatin, but other suitable coating materials,such as certain soluble gums or gum resins, which are u not attacked bythe liquid incapsulated, may be used. Where it is desired to incapsulatean aqueous liquid, sheet gelatin of the type now available cannot beused, as it is dissolved by the aqueous liquid; but other sheet materialhaving the necessary elasticity and plasticity may be used.

The coating material may be readily produced in sheets of the requiredthickness, and within closely assigned limits of tolerance, e. g. withintolerances of 0.001 inch, readily, by flowing the material in a liquidstate on to a moving web or drum and under an accurately positioneddoctor.

knife, and subsequently passing the web through a suitable conditioningchamber or internally cooling the drum to harden the material thereon tothe desired degree of plasticity.

Various forms of apparatus may be used for the carrying out of theinvention, but whatever form of apparatus may be used, it is importantto provide means by which a suitable body of liquid may be maintainedabove the point of convergence of the two sheets of gelatin, the liquidbeing prevented from flowing past the point of convergence by properlycontrolling the depth of the depressions between the mold openings sothat those portions of the sheets of gelatin between the capsules whichare formed come into contact under pressure, forming a tight joint whichprevents any considerable amount of the liquid from flowing past thepoint of convergence.

The invention will be further described in connection with theaccompanying drawings, which illustrate, in a somewhat conventional anddiagrammatic manner, apparatus which embodies the invention and isadapted for the practice of the process of the invention.

In the drawings:

Fig. 1 is a transverse sectional view of a, portion of an apparatuswhich embodies the invention, showing two rotatable drums adapted to actas continuous molds;

Fig. 2 is a transverse sectional view of one of the drums illustrated inFig. 1;

Fig. 3 is a side view in elevation showing the two rotatable drums ofFig. 1;

Fig. 4 is a sectional view of portions of the two rotatable drums atthepoint of contact where the two sheets of coating material are forcedtogether and the capsules'are cut out;

Fig. 5 is a transverse sectional view of a modified apparatus whichembodies the invention in which one of the mold members is a rotatabledrum and the other is flat and composed of sections;

Fig. 6 is a side view in elevation of the rotatable mold member of theapparatus illustrated in Fig. 5;

Fig. 'I is a plan view with portions in section of the apparatusillustrated in Fig. 5;

Fig. 8 is a sectional view of one of the flat mold sections with itssupport; and

Fig. 9 is another sectional view of one of the flat mold sections withits support, showing the means by which a vacuum is applied to the sheetof coating material.

In the apparatus illustrated in Figs. 1 through 4, there are providedtwo rotatable drum-like mold members I 0 and I I, each provided withgear teeth I2 which mesh to insure that the two mold members rotate insynchronism.

Each of these mold members is provided with a series of female moldopenings l3 corresponding in size and shape to the size of the capsulesto be produced, each opening being provided with a raised cutting edgel5 and with depressed portions' l1 between these openings. The depth ofthe depressions I1 is carefully regulated so that it is about the sameas the thickness of the sheets of coating material, such as gelatin,which are to be used with the apparatus.

These rotatable mold members are supported on the shafts I9, to whichthey are keyed as at 2|, which shafts in turn are supported by the frame23. The mold members are rotated by means of a belt passing over thepulley 24, or in any other suitable way, the fact that each carriesinter-meshing gears insuring their synchronous rotation.

Each of the mold openings I3 is of a size and shape to correspond to theexterior of one-half of the desired finished capsule, and may behemispherical, as illustrated, or semi-ellipsoidal, or of other desiredshape. From the bottom of each of the mold openings there is a smallpassageway 25, communicating with conduits 21, which extends from anopen end at one side of the rotatable member to connect each of thedepressions I3 in a given row, so that when a vacuum is applied at theopen end of the conduit a. vacuum is produced within each of theinterconnected depressions or mold openings l3.

The passageways 25 are relatively small, so that when the sheet ofcoating material is drawn down into a mold opening IS a smooth surfaceddepression or recess is formed, and no part is drawn further into thepassageway 25 with the production of a protuberance. On the other hand,the passageways 25 are sufliciently large so that a vacuum is readilyproduced in the mold openings l3, and so that the passageways are notreadily clogged by a small particle of foreign matter. It will beevident that the size of these passageways must depend upon thethickness and hardness of the coating material used, being quite smallif a. thin sheet of relatively soft material is used, and larger if athick sheet of relatively hard material is used. These passageways servenot only as a means of producing a vacuum to preform the depressions orrecesses in the sheets of coating material, but also serve as conduitsor passageways through which compressed air may be introduced into themold openings to force the finished capsules out, to avoid anypossibility of their sticking after they have been finished.

The end surface of the drums at which the conduits 21 open are machined,and have a smooth surface. An open box 29, with the open side in tightcontact with the machined end of the drum, suitably connected byconduits 3| to vacuum, is provided on each drum, and is so located, asillustrated in Fig. 3, that a vacuum is produced within each of theopenings l3 about one-sixth of a revolution before the convergence ofthe two drums, the vacuum box being of suflicient length so that thevacuum is continued to about the point of convergence.

There is also provided a dam 33 at each end of the apparatus, which damserves to maintain a body of liquid above the point of convergence ofthe two rotatable drums. These dams are interlocked with the drums, asshown at 34, to minimize leakage, the liquid serving as alubricantbetween the sliding surfaces of the dams and the rotatable drums.

In operation, a body of liquid is maintained above the point ofconvergence of the two drums, between the dams 33, and two sheets ofcoating material are fed continuously to the apparatus, one at the topof each of the rotatable mold memcamera bers, as illustrated. As thedrum rotate, carrying with them the two sheets of coating material, eachrow of mold openings It comes successively into communication with thevacuum chambers 29, with the result that the coating material is drawndown into the mold openings with the formation of depressions orrecesses therein. As these depressions or recesses are formed, and asthey pass forward into and through the body of liquid maintained betweenthe dams, they become filled with liquid, care being taken that thelevel of the liquid is maintained sumciently high so that no air isentrapped in the recesses or depressions. The liquid level may becontrolled by an automatic float (not shown) manually, or in anysuitable way. As the mold openings progress forward, and the two sheetsconverge, the raised edges l5 around each of the mold openings serve tocompress the coating material between them and to cut it around each ofthe capsules which are formed, thus hermetically sealing together thetwo halves of each capsule.

The depressions Il between the mold openings are of'such depth as tojust accommodate the coating material, while compressing together thetwo sheets somewhat, so that no part of the liquid can flow down betweenthe mold openings thus preventing leakage.

There is also provided at the machined side of each of the drums achamber 35, placed below the point of contact of the two drums, similarto the vacuum chambers 29, but smaller in size and connected by conduits36 to a suitable course of compressed air, so that if any of thecapsules have a tendency to stick in the mold openings they are forcedout by the compressed air almost immediately after they have beenformed. v

The number of mold openings l3 which may be provided in each row alongan element parallel to the axis of each rotatable drum may be variedalmost at will, from one to any desired number, the practical limitationbeing fixed by the width of the strips of coating material which may becontinuously formed with accurately predetermined thickness, the numberillustrated being five. It will be apparent that by making the vacuumconduits 21 sufilciently large, it will be easily possible to producethe desired vacuum, which need only be of the order of a few inches ofmercury, in an almost indefinite number of mold openings in a singlerow.

In the apparatus more particularly illustrated in Figs. 5 through 9,there are provided, instead of two rotatable mold members, one rotatablemold member 40, and one flat mold member 42, made up in sections 44; Theconstruction of the rotatable mold member 40 is almost identical withthat of the rotatable mold members illustrated in Fig. 1, it beingprovided with suitable mold openings 46 of the desired shape and size,suitably connected by passageways 48 to conduits 59, open at one end ofthe rotatable mold member, which end is provided with a machined surface52, and closed at the other end. The mold openings are provided withraised cutting edges 54, and with depressed portions 56 between them,the depth of these depressions being regulated in accordance with thethickness of the sheets of coating material to be used.

The mold sections which constitute the flat mold member are alsoprovided with mold openings 59, which correspond to the openings 48 inportions between them. Each of these openings II is connected by apassageway 90 leading from its bottom to the bottom of the moldsections, so that there is a free passageway from each of the openings99 through to the bottom of the mold 5 sections.

Each of the fiat mold sections 44 is provided on each side with gearteeth 82 which mesh with the gear teeth 94 provided on the rotatablemold member and which insure that the forward in movement of the fiatmold sections and the rotational movement of the rotatable mold membersare synchronized, such that as the successive rows of mold openings inthe fiat sections come under the axis of the rotatable molds, a correllsponding row of openings of the rotatable m'old member reaches the samepoint, and a capsule is formed between each pair of openin s. The fiatmold sections are moved forward by the gear wheel 66, suitably driven,and serve to' drive 1 the rotatable mold member.

The rotatable mold member is supported on the frame 68, and rotates onthe axis I9 supported thereby. The fiat mold sections are supported bythe frame 12, fitting between the uprighti g5 flanges 14. A groove 16 isprovided at each side of each mold section, and a corresponding rib 18is provided at each side of the flange 12 so that as the mold sectionmoves forward over the vacuum chamber 80, the entrance of air along-thepoints of contact of the mold section and the frame into the vacuumchamber is minimized. Each' mold section is also provided at the frontend with a rib 82, which fits into a corresponding groove 84 provided atthe back of a each mold section, so that tight joints between the moldsections are insured.

The vacuum chamber 80, which is provided in the frame or support 12, isconnected by means of conduits 8| to a suitable vacuum device (notshown), and extends to a point about under the axis of the rotatablemold member. A vacuum chamber 95, similar to those provided on therotatable mold members of the apparatus of Figs. 1 through 4, isprovided at the side of the rotatable mold member which is provided witha machined surface, and at which the conduits 59 open. This vacuumchamber 85 extends from somewhat above .a horizontal diameter of arotatable mold member to a point about under its I axis, serving topreform recesses or depressions in the gelatin from a point somewhatabove the horizontal axis of the drum, and to maintain the recesses ordepressions properly formed until the capsules are finally sealed.

There is also provided a dam 86, which extends down in tight slidingengagement with the surface 89 provided at each side of the fiat moldsections, the dam being provided with a lip which fits into the groove90 at each side of each fiat mold section, to minimize leakage. The damN also is fitted in an interlocking manner, as shown at 92, to the sidesof therotatable mold member, to minimize leakage at the points of Icontact of the dam and the rotatable mold member. At the point ofcontact of the dam with the sheet of coating material which is carriedforward along the fiat mold member there is provided an apron 94, withthe edge with which the coating material first comes into contactsomewhat upraised as at 96 to prevent sticking, l0 and with the otheredge held in position by the f spring shoe 95, which exerts a properdownward pressure to insure tight contact between the apron and theshoe. This apron, which is somewhat wider than the distance betweenthree 1 rows of mold openings, serves to prevent leakage of the liquidalong the upper surface of the strip. The height of the dam is such thata body of liquid can be maintained between the converging strips ofcoating material which is sumcient to insure that when the depressionsor recesses are formed in the strip being carried forward by therotatable mold member, no air can be entrapped, and care should be takenthat the height of the liquid level is sufficient to prevent theentrapping of air. The liquid level may be maintained either by means ofan automatic float, or other automatic means, or it may be maintainedmanually.

A continuous sheet of coating material is fed to the flat mold memberalong the runway 88, passing under the roller I00 so that it lies flaton top of the mold member before passing under the apron 8| and beforecoming above the vacuum chamber. If it is found that the coatingmaterial has a tendency to stick to the apron 94, the roller i 00,instead of being a simple roller to insure that the coating material isflat on the mold member, may be an oiling roller, supplying lubricant tothe coating material to lubricate its passage under the apron. If thisroller is used as an oiling roller, care should be taken that thelubricant which is supplied thereby is of a nature which is compatiblewith the liquid which is being incapsulated, and which, when present inminute amounts in the finished capsule, has no deleterious effect. Inmany cases, it will be found desirable to use as a lubricant the samematerial which is being incapsulated, or a related material. As the moldmember, and the coating material, move forward over the vacuum chamber,a vacuum is produced within each row of hemispherical molds, eachconnected with a passageway 60 leading to the bottom of the mold membar,so that the air is withdrawn from the molds and the coating material isdrawn down into the molds forming a number of depressions or recessescorresponding in shape and size to the.

mold openings. As the thickness of the coating material is carefullycontrolled, the volume of the liquid which passes into the recesses ordepressions may be accurately predetermined and controlled. As thedepressions or recesses move forward with the mold member, they passunder the body of liquid which is maintained by the dam and thedepressions or recesses become full of the liquid.

Another continuous sheet of the coating material is fed to the rotatabledrum at about the top and is carried forward along with it as it rotatestoward the flat mold member. As the rotatable mold member rotates, themold openings 48 come into successive communication with the vacuumchamber 85, with the result that a depression or recess is formedcorresponding to each mold opening, and as the sheet of coating materialpasses down through the body of liquid which is maintained, thedepressions or recesses become full of liquid. As the drum rotates, andthe flat mold member moves forward, each row of recesses or depressionsin the sheet being carried by the,rotatable mold member comes over acorresponding row of depressions or recesses formed in the sheet on thefiat mold member,

and as the corresponding rows come under the axis of the rotatable moldmember, the two sheets of coating material are forced together, formingthe capsules, which are hermetically sealed and are cut from the sheetsof coating material. As the depressions between the openings arecarefully regulated as to depth to provide room only for the coatingmaterial, none of the liquid in the body can pass forward or leak pastthe point at which the capsules are formed and sealed.

A chamber I02, connected by conduit I, to a suitable source ofcompressed air, is provided in the frame 12 which supports the flat moldmember at a point subsequent to that at which the capsules are formed,and a similar chamber I08, connected by conduit III to a suitable sourceof compressed air, is provided to communicate with the conduits 50 ofthe rotatable member, subsequent to the point where the capsules areformed. These compressed air chambers are provided so that in the eventthat any of the capsules tend to stick in the mold openings after theyareformed, they will be forced out by the compressed air. I

After each section of .the flat mold member passes the rotatable moldmember, and the capsules are formed, it is removed from the suport 12,and returned to the other end of the apparatus; so that, in effect, theflat mold member is continuous.

It will thus be seen that by the present invention, I provide a methodand apparatus by which medicinal capsules provided with a liquid centersuitably coated with a coating of a tough, o

elastic, soluble material, such as sheet gelatin, and hermeticallysealed therein, the coating having a substantially uniform thicknessthroughout, and the volume of the liquid within the capsule beingaccurately determined, may be produced in a continuous manner and withapparatus which requires a minimum of attention.

I claim:

1. The continuous process of producing liquid filled capsules whichcomprises feeding a pair of sheets of elastic coating material inconverging paths, progressively and continuously subjecting each sheetto the action of a vacuum to perform depressions or recesses therein,each recess or depression in one sheet corresponding to one in theother, passing the sheets of coating material with the depressions orrecesses formed therein against a body of liquid maintained adjacent thepoint of convergence of the sheets of coating material to fill eachrecess or depression with liquid and eliminate all air therefrom, andprogressively and continuously cutting the sheets of material andapplying pressure thereto to cause the edges of the cut portions toadhere to form capsules, and substantially preventing the liquid fromflowing past the line of convergence of the sheets and from coming intocontact with the exterior of the capsules.

2. Apparatus for continuously producing liquid filled capsulescomprising a pair of continuously moving mold members, each providedwith a plurality of mold recesses in corresponding positions, a raisedcutting edge around each said recess, said mold members being adapted tocarry two continuous sheets of coating material in converging paths,means for applyinga vacuum within each mold recess at a position priorto the convergence of the two sheets of material to preformcorresponding recesses or depressions in each sheet of coating material,damming means for maintaining a body of liquid to be encapsulated aboveand adjacent to the point of convergence of the two sheets of coatingmaterial and for substantially preventing the liquid from flowing pastthe line of convergence of the sheets and from coming into contact withthe exterior of the capsules,

" a 219373 Y s ,5

and for synchronising the niovement 01 4. Apparatus as in claim 2, inwhich the mold the two mold members. openings are provided with raisedcutting edges 3. Apparatus as in claim 2, in which the mold withdepressions therebetween, the depth of said openings are of a size andshape to correspond depressions being substantially the same as the toone half of the desired exterior dimensions of thickness of the coatingmaterial to be used. the capsules.

' PAUL S. PITTENGER.

